title: Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy.
abstract: OBJECTIVE
  We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity.
  
  
  METHODS
  In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand).
  
  
  RESULTS
  Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = -0.66, p = 0.003) and more microbleeds (r = -0.78, p < 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08).
  
  
  CONCLUSIONS
  Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.
authors.affiliation: From the Department of Radiology, Seaman Family MR Centre (S.P., C.R.M., R.F., B.G.G., E.E.S.), Departments of Clinical Neurosciences (E.D., G.K., N.S., K.S., A.C., N.P., M.J.P., R.F., B.G.G., E.E.S.), Physiology and Pharmacology (C.D.S., A.B., D.F., M.J.P.), and Community Health Sciences (G.H.F., E.E.S.), University of Calgary, Canada; Institute of Human Movement Sciences and Sport (D.F.), ETH Zurich, Switzerland; Hotchkiss Brain Institute (M.J.P., R.F., B.G.G., E.E.S.), and Faculty of Kinesiology (M.J.P.), University of Calgary; Foothills Medical Centre, Alberta Health Services, Canada.
authors.forename: Stefano
authors.initials: S
authors.lastname: Peca
authors.forename: Cheryl R
authors.initials: CR
authors.lastname: McCreary
authors.forename: Emily
authors.initials: E
authors.lastname: Donaldson
authors.forename: Gopukumar
authors.initials: G
authors.lastname: Kumarpillai
authors.forename: Nandavar
authors.initials: N
authors.lastname: Shobha
authors.forename: Karla
authors.initials: K
authors.lastname: Sanchez
authors.forename: Anna
authors.initials: A
authors.lastname: Charlton
authors.forename: Craig D
authors.initials: CD
authors.lastname: Steinback
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Beaudin
authors.forename: Daniela
authors.initials: D
authors.lastname: Flück
authors.forename: Neelan
authors.initials: N
authors.lastname: Pillay
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Fick
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Poulin
authors.forename: Richard
authors.initials: R
authors.lastname: Frayne
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Goodyear
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smith
mesh_terms: D000368:Aged; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology*; D002245:Carbon Dioxide / Q000008:administration & dosage; D016657:Cerebral Amyloid Angiopathy / Q000175:diagnosis / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000502:physiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004569:Electroencephalography; D005074:Evoked Potentials, Visual / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D002245:Carbon Dioxide; D010100:Oxygen